Excessive ROS production and enhanced autophagy contribute to myocardial injury induced by branched-chain amino acids: Roles for the AMPK-ULK1 signaling pathway and α7nAChR.

BACKGROUNDS AND AIMS: Leucine, isoleucine, and valine are diet derived and essential amino acids that are termed branched-chain amino acids (BCAA). BCAA are widely used as dietary supplements to boost muscle growth and enhance exercise performance. However, the effects of BCAA on myocardial function are largely unknown. This study was designed to investigate whether BCAA affect heart function and, if so, to further explore the underlying molecular basis for the observed effects. METHODS AND RESULTS: C57BL/6J mice were randomly divided into two groups, the control group received solvent (water) and the BCAA group received 2% BCAA dissolved in water, for a successive period of 12 weeks. Compared with control, BCAA treatment significantly increased water consumption without changing body weight or diet consumption; heart tissue BCAA levels were increased, markers representative of myocardial injury in heart tissue including c-reactive protein and cardiac muscle troponin were increased ; and creatine kinase, creatine kinase-MB, and lactate dehydrogenase were increased in serum; severe myocardial fibrosis was observed by Masson staining, which was accompanied by increased reactive oxygen species (ROS) production and decreased superoxide dismutase activity in heart tissue; both p-AMPK and p-ULK1 were significantly increased as was autophagy, judged by the presence of LC3 by western blotting and immunofluorescence, increased numbers of autophagosomes were found by transmission electron microscopy in the BCAA group. In vitro, 20 mmol/L BCAA significantly decreased cell viability and increased the production of ROS, as well as the expression of p-AMPK/AMPK and p-ULK1/ULK1 in cultured H9C2 cells. Treatment with the ROS scavenger N-acetyl-L-cysteine (NAC) improved cell viability and reversed ROS changes. Decreased H9C2 cell viability induced with 20 mmol/L BCAA was reversed by either blocking AMPK or inhibition of ULK1. Furthermore, blocking AMPK significantly decreased p-ULK1/ULK1, while inhibition of ULK1 reversed the enhanced expression of LC3-II/LC3-I induced by BCAA. Excessive ROS production and decreased cell viability induced by BCAA were further confirmed in primary cultured murine cardiomyocytes. Pharmacological activation of α7nAChR with PNU-282987 attenuated BCAA-induced injury in primary murine cardiomyocytes. However, this compound failed to suppress BCAA activation of AMPK and autophagy (LC3-II/I ratio). CONCLUSION: These results provide the first evidence that treatment of mice with BCAA induced myocardial injury by triggering excessive ROS production and by enhancing AMPK-ULK1 pathway-dependent autophagy. These findings suggested that inhibition of either ROS production or autophagy may alleviate myocardial injury induced by BCAA.

Biosynthesis of copper oxide nanoparticles and their potential synergistic effect on alloxan induced oxidative stress conditions during cardiac injury in Sprague-Dawley rats.

Cistus incanus leaf extract was used to biologically synthesize Copper oxide nanoparticles (CuO NPs). The characteristic UV-vis spectral band of CuO NPs found at 290 nm revealed the successful formation of CuO NPs. By the analysis of TEM and SEM, it is confirmed that the obtained CuO NPs were in spherical structure. By the analysis of Fourier transform infrared (FTIR) spectroscopy, it is evident that the absorption peak was situated at a position of about 480 cm-1 of wavenumber, which is typically considered as an extremely pure CuO NPs. The images of Transmission Electron Microscopy exhibited that the formed CuO NPs were in the size of about 15-25 nm and were relatively uniform in distribution. When related with the treatment of nanomaterials only, the synergistic interaction among CuO NPs and oxidative stress conditions considerably decreased the cardiac-related function catalogs, which includes pathological progressions of myocardium along with an obvious rise in the levels of creatine kinase-MB and cardiac troponin I. When compared to the void reaction of micro-CuO and cardiac operations in alloxan-injected rats, aggravation in the conditions of oxidative stress could be playing a significant part in the heart injury after dual exposing CuO NPs and alloxan. By these results, it is confirmed that the conditions of oxidative stress improved the contrary effects of CuO NPs to the heart, signifying that the utilization of nanomaterials in conditions of stress such as, in the delivery of drug, required to be cautiously monitored.

Shengjiang Powder ameliorates myocardial injury in septic rats by downregulating the phosphorylation of P38-MAPK.

Sepsis is the systemic inflammatory response caused by infection. Cardiac dysfunction is an acknowledged result of sepsis. Shengjiang Powder, a prescribed traditional Chinese medicine, showed anti-infection and antipyretic functions in our previous study. In this study, we established a septic rat model via cecal ligation puncture (CLP) to evaluate the effects of Shengjiang Powder on sepsis and the involvement of P38 mitogen activated protein kinase (P38-MAPK) signaling. The 10 main ingredients of Shengjiang Powder were identified by LC-MS. The results of this study indicated that Shengjiang Powder at a concentration of 3.0 g/kg with SB203580 (an inhibitor of P38-MAPK) could improve myocardial injury, ameliorate the histopathological abnormalities, decrease apoptosis and upregulate proliferating cell nuclear antigen (PCNA) levels in myocardial tissues. Further, cytokine mRNA expression levels (tumor necrosis factor - alpha, TNF-α and interleukin 6, IL-6) were decreased by Shengjiang Powder and SB203580 in the myocardial tissues. Furthermore, the p-P38 protein level in myocardial tissues was upregulated in septic rats but decreased upon treatment with Shengjiang Powder and SB203580; however, the relative protein level of P38 showed no significant changes. Collectively, Shengjiang Powder showed a myocardial protective effect on rats with CLP-induced sepsis.

Omega-3 PUFA attenuate mice myocardial infarction injury by emerging a protective eicosanoid pattern.

Omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation is a recommended preventive approach against cardiovascular diseases, but its mechanism of protection against myocardial infarction (MI) injury is not fully understood. Eicosanoid metabolomics demonstrated an abnormal eicosanoid profile was in the plasma of mice receiving MI surgery. 19,20-EDP, 17,18-EEQ, 14,15-EET and 9,10-EpOME were decreased, and PGE2 was increased by the surgery. N-3 PUFA-rich diets feeding or transgene of Fat-1 shifted the eicosanoid profile to an n-3 PUFA dominant style and attenuated the myocardial infarction injury. Multiple logistic regression analysis suggested the degree of MI injury was related with an eicosanoid pattern, composed by eicosanoids derived from both n-3 and n-6 PUFA in the three enzymatic pathways. These results suggested the benefits of n-3 PUFA on MI was achieved synergistically.

AIM2 Co-immunization with VP1 Is Associated with Increased Memory CD8 T Cells and Mounts Long Lasting Protection against Coxsackievirus B3 Challenge.

The recurrent Coxsackievirus B3 (CVB3) infection is the most important cause of intractable myocarditis which often leads to chronic myocarditis and even dilated cardiomyopathy. Therefore, enhanced DNA vaccines capable of memory CD8 T cells are essential for long-lasting immunological protection against CVB3 infection. In this study, absent in melanoma 2 (AIM2) was used as an adjuvant to enhance the induction of memory CD8 T cells elicited by VP1 (viral capsid protein 1) vaccine. Mice were intramuscularly injected with 50 µg AIM2 plasmid and equal amount of VP1 plasmid (pAIM2/pVP1) vaccine 4 times at 2 week-intervals. We observed that the protection of pAIM2/pVP1 vaccine against CVB3 challenge was evidenced by significantly improved cardiac function, reduced myocardial injuries, and increased survival rate when compared with immunization with pVP1. Co-immunization with pAIM2/pVP1 robustly augmented T lymphocytes proliferation and CVB3-specific cytotoxic T lymphocyte responses. Importantly, 16 weeks after the last immunization, pAIM2/pVP1 co-immunization significantly enhanced the expression of Bcl-6, SOCS3, and Sca-1 which are critical for memory CD8 T cells as compared with pVP1 immunization. Notably, CD8 T cells that are likely vaccine-induced memory T cells were responsible for the protective efficacy of pAIM2/pVP1 vaccine by abolition of a CD8 T cell immune response following a lethal dose of CVB3 infection. Our results indicate that AIM2-adjuvanted vaccine could be a potential and promising approach to promote a long-lasting protection against CVB3-induced myocarditis.

Oral glutamine reduces myocardial damage after coronary revascularization under cardiopulmonary bypass. A randomized clinical trial.

BACKGROUND: Glutamine is the most abundant free amino acid in the body. It modulates immune cell function and is an important energy substrate for cells in critically ill patients. Reduction of injury cardiac markers had been observed in patients receiving intravenous glutamine and in a pilot study with oral glutamine. The aim of this study was to analyze the effect of preoperative oral supplementation of glutamine on postoperative serum levels of cardiac injury markers. METHODS: A randomized clinical trial was performed in 28 Mexican patients with ischemic heart disease who underwent cardiopulmonary bypass with extracorporeal circulation. Patients were randomly assigned to receive oral glutamine (0.5 g/kg/day) or maltodextrin 3 days before surgery. Cardiac injury markers as troponin-I, creatine phosphokinase, and creatine phosphokinase-Mb were measured at 1, 12, and 24 hours postoperatively. RESULTS: At 12 and 24 hours serum markers levels were significantly lower in the glutamine group compared with controls (p = 0.01 and p = 0.001, respectively) (p = 0.004 and p < 0.001, respectively). Overall, complications were significantly lower in the glutamine group (p = 0.01, RR = 0.54, 95% CI 0.31-0.93). Mortality was observed with 2 cases of multiple organ failure in control group and 1 case of pulmonary embolism in glutamine group (p = 0.50). CONCLUSION: Preoperative oral glutamine standardized at a dose of 0.5 g/kg/day in our study group showed a significant reduction in postoperative myocardial damage. Lower cardiac injury markers levels, morbidity and mortality were observed in patients receiving glutamine.

Delonix regia Leaf Extract (DRLE): A Potential Therapeutic Agent for Cardioprotection.

Delonix regia (Boj. Ex. Hook) is a flowering plant in the pea family found in tropical areas and its leaves are used informally to treat diseases in folk medicine. However, the cardioprotective effects in this plant are still unclear. In this study, we found that the Delonix regia leaf extract (DRLE) (400 mg/kg/d) can reduce the mortality rate in an isoproterenol (ISO)-induced heart injury and hypertrophy mouse model. Decreased serum levels of creatine phosphokinase, LDH, GOT, TNF-alpha and increased nitric oxide levels were found in DRLE-treated ISO-injured mice. In the in vitro study, the porcine coronary artery exhibited vasodilation effect induced by DRLE in a dose-dependent manner. In the DRLE toxic test, overdose of DRLE showed the high safety in normal mice and may have the ability to remove the metabolic wastes in blood. In conclusion, we demonstrated for the first time that DRLE has the cardioprotective effects by activating the vasodilation through NO pathway and preventing the myocyte injury via inhibition of TNF-alpha pathway. We suggest that DRLE may act as a promising novel herbal medicine for cardioprotection.

Blueberry Anthocyanins-Enriched Extracts Attenuate Cyclophosphamide-Induced Cardiac Injury.

We sought to explore the effect of blueberry anthocyanins-enriched extracts (BAE) on cyclophosphamide (CTX)-induced cardiac injury. The rats were divided randomly into five groups including normal control, CTX 100 mg/kg, BAE 80mg/kg, CTX+BAE 20mg/kg and CTX+BAE 80mg/kg groups. The rats in the three BAE-treated groups were administered BAE for four weeks. Seven days after BAE administration, rats in CTX group and two BAE-treated groups were intraperitoneally injected with a single dose of 100 mg/kg CTX. Cardiac injury was assessed using physiological parameters, Echo, morphological staining, real-time PCR and western blot. In addition, cardiotoxicity indices, inflammatory cytokines expression and oxidative stress markers were also detected. Four weeks 20mg/kg and 80mg/kg dose of BAE treatment following CTX exposure attenuated mean arterial blood pressure, heart rate and activities of heart enzymes, improved cardiac dysfunction, left ventricular hypertrophy and fibrosis. Importantly, BAE also attenuated CTX-induced LV leukocyte infiltration and inflammatory cytokines expression, ameliorated oxidative stress as well as cardiomyocyte apoptosis. In conclusion, BAE attenuated the CTX-induced cardiac injury and the protective mechanisms were related closely to the anti-inflammatory, antioxidant and anti-inflammatory characteristics of BAE.

Naja naja karachiensis envenomation: biochemical parameters for cardiac, liver, and renal damage along with their neutralization by medicinal plants.

Naja naja karachiensis envenomation was found to hit more drastically heart, liver, and kidneys. 400 µg/kg of venom-raised moderate serum levels of ALT (72 ± 4.70 U/L, 0.1 > P > 0.05), AST (157 ± 24.24 U/L, 0.1 > P > 0.05), urea (42 ± 3.08 mg/dL, 0.05 > P > 0.02), creatinine (1.74 ± 0.03 mg/dL, 0.01 > P > 0.001), CK-MB (21 ± 1.5 U/L, 0.05 > P > 0.02), and LDH (2064 ± 15.98 U/L, P < 0.001) were injected in experimental rabbits. However, lethality was enhanced with 800 µg/kg of venom in terms of significant release of ALT (86 ± 5.0 U/L, 0.05 > P > 0.02), AST (251 ± 18.2 U/L, 0.01 > P > 0.001), urea (57.6 ± 3.84 mg/dL, 0.02 > P > 0.01), creatinine (2.1 ± 0.10 mg/dL, 0.02 > P > 0.01), CK-MB (77 ± 11.22 U/L, 0.05 > P > 0.02), and LDH (2562 ± 25.14 U/L, P ≪ 0.001). Among twenty-eight tested medicinal plant extracts, only Stenolobium stans (L.) Seem was found the best antivenom (P > 0.5) compared to the efficacy of standard antidote (ALT = 52.5 ± 3.51 U/L, AST = 69.5 ± 18.55 U/L, urea = 31.5 ± 0.50 mg/dL, creatinine = 1.08 ± 0.02 mg/dL, CK-MB = 09 ± 0.85 U/L, and LDH = 763 ± 6.01 U/L). Other plant extracts were proved less beneficial and partly neutralized the toxicities posed by cobra venom. However, it is essential in future to isolate and characterize bioactive compound(s) from Stenolobium stans (L.) Seem extract to overcome the complications of snake bite.

Oxymatrine protects against myocardial injury via inhibition of JAK2/STAT3 signaling in rat septic shock.

Oxymatrine (OMT), an alkaloid extracted from Sophora japonica (kushen), is used to treat inflammatory diseases and various types of cancer in traditional Chinese medicine. However, the cellular and molecular mechanisms underlying the anti­inflammatory activity of OMT remain poorly understood. The present study explored the protective effect of OMT on myocardial injury in rats with septic shock by inhibiting the activation of the janus kinase­signal transducer and activator of transcription (JAK/STAT) signaling pathway. OMT treatment was found to significantly inhibit the activation of JAK2 and STAT3 in myocardial tissue. It also attenuated the expression of pro­inflammatory cytokines, including interleukin­1ß and tumor necrosis factor­α. In addition, OMT exhibited anti­inflammatory properties as heart function and myocardial contractility was improved and pathological and ultrastructural injury was prevented in myocardial tissue induced by septic shock. The results indicate that OMT exhibits substantial therapeutic potential for the treatment of septic shock­induced myocardial injury through inhibition of the JAK2/STAT3 signaling pathway.

Tropisetron attenuates cardiac injury in a rat trauma-hemorrhage model.

Tropisetron is widely used for antiemesis. Recent evidence shows that tropisetron possesses anti-inflammatory properties. Protein kinase B (Akt) is known to play an important role in negating proinflammatory response in injury. The aim of this study was to determine whether tropisetron provides cardioprotection mediated via an Akt-dependent pathway in trauma-hemorrhaged animals. Male Sprague-Dawley rats underwent trauma-hemorrhage and resuscitation. Tropisetron (1 mg/kg) with or without a PI3K inhibitor (wortmannin, 1 mg/kg) or vehicle was administered intravenously during the resuscitation. At 24 h after either the trauma-hemorrhage or sham operation, the cardiac function parameters (cardiac output, left ventricle pressure variability) were measured. Cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, Akt activity, and apoptosis were measured. One-way analysis of variance and Tukey test were used for statistical analysis. Cardiac function was depressed and cardiac myeloperoxidase activity, interleukin 6 and intercellular adhesion molecule 1 levels, and cardiac apoptosis were markedly increased after trauma-hemorrhage. Administration of tropisetron significantly improved cardiac function and proinflammatory parameters in the tropisetron-treated rats subjected to trauma-hemorrhage. The increase in cardiac apoptosis was attenuated in rats that received tropisetron. Although trauma-hemorrhage decreased cardiac Akt phosphorylation (p-Akt), tropisetron treatment prevented the same decrease in cardiac p-Akt following trauma-hemorrhage. Coadministration of wortmannin prevented the beneficial effects of tropisetron on the attenuation of proinflammatory responses and cardiac injury after trauma-hemorrhage. Tropisetron attenuates cardiac injury following trauma-hemorrhage, which is, at least in part, through Akt-dependent anti-inflammatory pathway.

Myocardial mitochondrial injury induced by pulmonary exposure to particulate matter in rats.

Exposure to air pollution has been associated with acute myocardial ischemia, impaired myocardrial function, and ST-segment depression. Particulate matter (PM)-associated metals, especially vanadium and nickel, have been implicated in observed cardiovascular impairments. We aimed to assess the effect of single intratracheal pulmonary exposure to vanadium-rich respirable oil combustion PM (HP-10) on the intrinsic myocardial ischemic tolerance and mitochondrial integrity in rats. The authors subjected isolated heart tissue slices derived from saline or PM-exposed rats to low glucose low oxygen induced ischemia followed by oxygenated condition with glucose supplementation. Mitochondrial structural integrity was determined by TEM (transmission electron microscopy) and functionality by the 3-(4, 5 dimethylthiazol-2yl)-2, 5 diphenyltetrazolium bromide (MTT) assay. Rats exposed to PM exhibited no apparent inhibition of mitochondrial dehydrogenase activity in oxygenated conditions at 24 or 48 hr post-PM exposure. However, in conditions of simulated ischemia/reoxygenation, these heart slices showed a delayed but consistent and significant decrease in dehydrogenase activity compared to controls at 48 hr after exposure to PM. Electron microscopy revealed significant myocardial mitochondrial injury upon exposure to PM characterized by mitochondrial swelling and fusion. The authors conclude that exposure to soluble vanadium-rich PM induces mitochondrial functional impairment and structural abnormality, which compromises mitochondrial respiration and results in decreased tolerance to ischemia/reoxygenation in rats.

Secreted phospholipase A2 revisited.

Phospholipase A(2) (PLA(2)) catalyses the hydrolysis of the sn-2 position of glycerophospholipids to yield fatty acids and lysophospholipids. So far, more than 30 enzymes that possess PLA(2) or related activity have been identified in mammals. About one third of these enzymes belong to the secreted PLA(2) (sPLA(2)) family, which comprises low molecular weight, Ca(2+) requiring, secreted enzymes with a His/Asp catalytic dyad. Individual sPLA(2)s display distinct localizations and enzymatic properties, suggesting their specialized biological roles. However, in contrast to intracellular PLA(2)s, whose roles in signal transduction and membrane homoeostasis have been well documented, the biological roles of sPLA(2)s in vivo have remained obscure until recently. Over the past decade, information fuelled by studies employing knockout and transgenic mice as well as specific inhibitors, in combination with lipidomics, has clarified when and where the different sPLA(2) isoforms are expressed, which isoforms are involved in what types of pathophysiology, and how they exhibit their specific functions. In this review, we highlight recent advances in PLA(2) research, focusing mainly on the physiological functions of sPLA(2)s and their modes of action on 'extracellular' phospholipid targets versus lipid mediator production.

Protective effects of Salvia miltiorrhizae on the hearts of rats with severe acute pancreatits or obstructive jaundice.

OBJECTIVE: To investigate the therapeutic effects and mechanisms of Salvia miltiorrhizae (Danshen) in the treatment of severe acute pancreatitis (SAP)- or obstructive jaundice (OJ)-induced heart injury. METHODS: A total of 288 rats were used for SAP- (n=108) and OJ-associated (n=180) experiments. The rats were randomly divided into sham-operated, model control, and Salvia miltiorrhizae-treated groups. According to the difference of time points after operation, SAP rats in each group were subdivided into 3, 6 and 12 h subgroups (n=12), whereas OJ rats were subdivided into 7, 14, 21, and 28 d subgroups (n=15). At the corresponding time points after operation, the mortality rates of the rats, the contents of endotoxin and phospholipase A2 (PLA2) in blood, and pathological changes of the hearts were investigated. RESULTS: The numbers of dead SAP and OJ rats in the treated groups declined as compared with those in the model control group, but not significantly (P>0.05). The contents of endotoxin (at 6 and 12 h in SAP rats and on 7, 14, 21, and 28 d in OJ rats, respectively) and PLA2 (at 6 and 12 h in SAP rats and on 28 d in OJ rats, respectively) in the treated group were significantly lower than those in the model control group (P<0.01 and P<0.001, respectively). Besides, myocardial pathological injuries were mitigated in SAP and OJ rats. CONCLUSION: In this study, we found that Salvia miltiorrhizae improved myocardial pathological changes, reduced the content of PLA2 in blood, and decreased the mortality rates of SAP and OJ rats, exerting protective effects on the hearts of the rats.

Modification of alterations in cardiac function and sarcoplasmic reticulum by astragaloside IV in myocardial injury in vivo.

Astragaloside IV, the primary pure saponin isolated from Astragalus membranaceus has been found to have potent cardioprotective effects. In this study, we aim to investigate if the beneficial effects of astragaloside IV on cardiac function are associated with improvement in sarcoplasmic reticulum Ca(2+)-pump function in myocardial injury in vivo. Myocardial injury in rats was induced by subcutaneous injection of a high dose of isoproterenol, and the therapeutic effect of astragaloside IV was observed. Isoproterenol-treated rats showed widespread subendocardial necrosis, a rise in serum lactate dehydrogenase and creatine kinase, formation of lipid oxide product malondialdehyde and inhibition of left ventricular diastolic and systolic function, which suggested severe myocardial injury and acute heart failure. Moreover, sarcoplasmic reticulum Ca(2+)-uptake ability and Ca(2+)-ATPase (SERCA2a) activity were significantly reduced. And the level of SERCA2a mRNA and protein expression was also markedly decreased, associated with a decrease in Ser(16)-phosphorylated phospholamban protein expression, while total phospholamban level was unchanged in the isoproterenol-treated group compared with controls. However, these biochemical and hemodynamic changes in the acute failing hearts were prevented by treatment of isoproterenol-induced rats with astragaloside IV. Likewise, the observed reductions in sarcoplasmic reticulum Ca(2+)-pump function as well as in SERCA2a mRNA and protein levels and the phosphorylation level of phospholamban in the injured hearts were attenuated by astragaloside IV treatment. These results suggest that the beneficial effect of astragaloside IV on isoproterenol-induced myocardial injury may be due to its ability to prevent changes of SERCA2a and Ser(16)-phosphorylated phospholamban protein expression and, thus, may prevent the depression in sarcoplasmic reticulum Ca(2+) transport and improve cardiac function.

Effect of triiodothyronine administration in experimental myocardial injury.

Twelve healthy pigs were subjected to a 20-min, period of regional myocardial ischemia by snaring the left anterior descending coronary artery (LAD) between its first and second diagonal branches. The resulting myocardial injury caused significant acute hemodynamic impairments. Cardiac index declined significantly during reperfusion interval and returned to preischemic level by postoperative day 7. Plasma total triiodothyronine (TT3), free triiodothyronine (FT3) and free fatty acid (FFA) decreased gradually and reached the nadir at 6 h after LAD occlusion. In contrast, plasma reverse triiodothyronine (rT3) increased progressively after LAD occlusion and reperfusion. To investigate the effect of T3 on ischemic myocardium, T3 (0.2 microgram/kg/dose; n = 5) or saline (placebo; n = 6) was administered immediately, 30 min, 60 min, 90 min, and 120 min after reperfusion. Plasma TT3 and FT3 increased dramatically after triiodothyronine supplement but declined to presichemic level at six h after LAD occlusion. The pigs treated with T3 demonstrated a rapid improvement in cardiac index over the reperfusion interval, whereas cardiac index in the placebo group remained depressed. Myocardial oxygen consumption estimated by rate pressure product showed no difference between placebo and T3-treated groups. Oxygen extraction as O2 saturation difference between aorta and coronary sinus was less in T3-treated group. Nine pigs (four in the T3-treated group and five in the placebo group) were subjected to euthanasia with hypertonic KCl solution on postoperative day 7. Myocardial infarct size determined by triphenyltetrazolium chloride (TTC) tissue enzyme staining technique was not significantly different between T3-treated and placebo groups. We concluded that this animal model is a useful model of myocardial injury simulating "euthyroid sick syndrome" as seen in patients with cardiopulmonary bypass, and T3 supplementation after reperfusion significantly enhanced postischemic left ventricular functional recovery but did not affect myocardial oxygen consumption and myocardial infarct size.